This proposal is prepared by a group of molecular cell biologists (Giulia Baldini, M.D./Ph.D.; Jon Dranoff, M.D.; Vladimir Lupashin, Ph.D.; Peter M. Price, Ph.D; Sung Rhee, Ph.D.; Brian Storrie, Ph.D.; and Haibo Zhao, M.D./Ph.D.). Each, as part of their research, uses imaging approaches to answer questions and resolve hypotheses. The work ranges from i) basic cell biology of secretion to ii) diabetes and protein folding disorders to iii) liver fibrosis, to iv) hypertension and bleeding disorders and v) bone remodeling The research has common themes and approaches in molecular cell biology and imaging. As appropriate for the range of applications, the research is supported by 4 different NIH Institutes: NIGMS, NIAMS, NIDDK, and NHLBI. In all of our work, obtaining high spatial resolution is important and a current challenge to progress in our respective fields. Thus this common need has drawn us together to propose obtaining a new technology microscope system with higher resolution than is currently available in our laboratories. In sum, based on our preliminary studies, we find that 3D-structured illumination microscopy (3D-SIM) combined with PALM/STORM in a single microscope can provide biologically significant and unprecedented improvements in resolution that we can apply immediately to our individual laboratory efforts. We find the Zeiss ELYRA PS.1 microscope to be a compelling choice for our needs and research progress and therefore request funds to purchase and partially pay the required 8.5% local sales tax.